Abstract
The neurodevelopmental exposome paradigm was applied on a cohort of mother-infant pairs (n=178). Prenatal exposure to metals and metalloids was determined by measuring mercury in hair samples selected at birth, while cord blood and breast milk samples were analysed for mercury, cadmium, lead, and arsenic, as well as for essential elements (selenium, zinc, copper). Cognitive function, language, and motor development were assessed in children at the age of 18 months by the Bayley Scale for Infant Development (Bayley-III) development tool. The individual-level biological profiles were characterized using both nuclear magnetic resonance (NMR) spectroscopy and ultra‐high-performance liquid chromatography‐high resolution mass spectrometry (UPLC‐HRMS) for the untargeted urinary and plasma metabolomics analysis. LC-HRMS metabolites were assigned using the xcms and CAMERA R packages. In this study Human Metabolome DataBase (HMDB), Metlin, and LipidMaps databases were used for annotations, considering the calculated mass error in ppm, the isotope patterns, and the MS spectra. NMR spectra were preprocessed with MestreNova v.11.04 and ChenomX 8.03. Integrated pathway analysis and exposome-wide association algorithms were used for the evaluation of the associations between in utero exposure to metals and metabolic pathway dysregulation, as well as between metabolic pathway perturbations and neurodevelopment. NMR and UPLC‐HRMS analysis of plasma samples, as well as the analysis of urine samples pointed out the presence of oxoglutaric acid, oxalosuccinic acid, succinate, 2-oxoglutarate, formate, isocitrate, oxoglutaric acid, glycerol, L-carnitine, glutathione, methionine, cysteine, pyruvate, N-acetylglutamic acid, β-alanine, serine, and arginine. Τherefore, pathway analysis revealed that the most perturbed metabolic pathways from exposure to heavy metals were related to TCA cycle, purine, pyrimidine, phospholipids and carnitine metabolism, and glycolysis. The aforementioned results suggested major disturbances to cell biochemistry, which resulted in the impairment of antioxidant defense mechanisms leading to the clinically observed results in linguistic, motor development and cognitive capacity.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
